GZGD03109 EDGE: A Phase 3, Randomized, Multi-Center, Multi-National, Double-Blind Study to Evaluate the Efficacy, Safety, and Pharmacokinetics of Once Daily versus Twice Daily Dosing of Genz-112638 in Patients with Gaucher Disease Type 1 who have De

Brief Summary

This is a Phase 3, randomized, multi-center, multi-national, double-blind study to evaluate the efficacy, safety, and pharmacokinetics of QD versus BID Genz-112638 in male and female patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638.

The primary objective of this study is to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of Genz-112638 in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638. The secondary objective is to evaluate the pharmacokinetics (PK) of Genz-99067 when Genz-112638 is administered QD and BID in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638.The primary objective of this study is to evaluate the efficacy and safety of once daily (QD) versus twice daily (BID) dosing of Genz-112638 in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638. The secondary objective is to evaluate the pharmacokinetics (PK) of Genz-99067 when Genz-112638 is administered QD and BID in patients with Gaucher disease type 1 who have demonstrated clinical stability on BID dosing of Genz-112638.

Contact Information

Patients must meet all of the following inclusion criteria in order to participate in this study:

1. The patient is willing and able to provide signed informed onsent prior to any study-related procedures.

2. The patient is ≥18 years of age.

3. The patient has a diagnosis of Gaucher disease type 1 confirmed by a documented deficiency of acid β-glucosidase activity by enzyme assay. The patient may be previously untreated, off prior treatment, or receiving enzyme replacement therapy for Gaucher disease.

4. The patient meets all of the following criteria at the time of Screening:

• Hemoglobin level ≥9 g/dL (mean of 2 measurements);

• Platelet count ≥70,000/mm3 (mean of 2 measurements);

• Spleen volume ≤25 MN;

• Liver volume ≤2.0 MN.

5. The patient consents to provide a blood sample for genotyping for Gaucher disease and for CYP2D6 to categorize the patient’s predicted rate of metabolism, if these genotyping results are not already available for the patient.

6. Female patients of childbearing potential must have a documented negative pregnancy test prior to administration of the first dose of Genz-112638 in this study. In addition, all female patients of childbearing potential must use a medically accepted form of contraception throughout the study, i.e., either a barrier method or hormonal contraceptive with norethindrone and ethinyl estradiol or similar active components.

7. The patient is willing to abstain from consumption of grapefruit, grapefruit juice, or grapefruit products for 72 hours prior to administration of the first dose of Genz-112638 and throughout the duration of the study.

1. The patient is participating in GZGD02607 study, “A Phase 3, Randomized, Multi-Center, Multi-National, Open-Label, Active Comparator Study to Evaluate the Efficacy and Safety of Genz-112638 in Patients with Gaucher Disease Type 1 who have been Stabilized with Cerezyme®,” or is eligible for inclusion in GZGD02607 (while enrollment is ongoing) and has access to a physician participating in GZGD02607.

OR

The patient is participating in GZGD02507 study, “A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study Confirming the Efficacy and Safety of Genz-112638 in Patients with Gaucher Disease Type 1,” or is eligible for inclusion in GZGD02507 (while enrollment is ongoing) and has access to a physician participating in GZGD02507.

2. The patient received miglustat within 6 months prior to administration of the first dose of Genz-112638 in this study.

3. The patient has had a partial or total splenectomy within 3 years prior to administration of the first dose of Genz-112638 in this study.

6. The patient has a documented deficiency of iron, vitamin B-12, or folate that requires treatment not yet initiated or, if initiated, the patient has not been stable under treatment for at least 3 months prior to administration of the first dose of Genz-112638 in this study.

(including hypokalaemia or hypomagnesemia), or psychiatric disease, other medical conditions, or serious intercurrent illnesses that may preclude participation in the study.

9. The patient is known to have any of the following: Clinically significant coronary artery disease including history of myocardial infarction [MI] or ongoing signs or symptoms consistent with cardiac ischemia or heart failure; or clinically significant arrhythmias or

10. The patient is known to have tested positive for the human immunodeficiency virus (HIV) antibody, Hepatitis C antibody, or Hepatitis B surface antigen.

11. The patient has received an investigational product (other than Genz-112638) within 30 days prior to administration of the first dose of Genz-112638 in this study.

12. The patient is scheduled for in-patient hospitalization, including elective surgery, during the study.

13. The patient has a history of cancer, with the exception of basal cell carcinoma, within 5 years prior to administration of the first dose of Genz-112638 in this study.

14. The patient is pregnant or lactating.

15. The patient has received any medication that may cause QTc interval prolongation within 30 days prior to the first dose of Genz-112638. Exception: Diphenhydramine (Benadryl) or other medications used as premedication for ERT infusions are allowed up to 7 days prior to the first dose of Genz-112638.

16. The patient has received for the first time (i.e., the patient is not already chronically using) any of the following medications within 30 days prior to the first dose of Genz-112638:

• Strong inhibitors of CYP2D6 or CYP3A4;

• Inducers of CYP3A4.

17. The patient is a CYP2D6 non-poor metabolizer or an indeterminate metabolizer with one allele identified as active who is chronically receiving both a strong competitive inhibitor of CYP2D6 and a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.

OR

The patient is a CYP2D6 poor metabolizer or an indeterminate metabolizer with neither allele known to be active who is chronically receiving a strong competitive inhibitor of CYP3A4 and for whom no reasonable alternative medication exists.

Exception for both cases: Premedications for ERT infusions are allowed up to 7 days prior to the first dose of Genz-112638.